Therapeutic Bacterial Composition

Abstract

The invention relates to bacterial compositions useful in the treatment of cancer. In particular, the compositions can be used as a co-therapy with an immune checkpoint therapy. The invention also relates to methods for identifying a subject that will respond to therapy with an immune checkpoint inhibitor comprising determining the abundance of bacteria in a biological sample from said subject.

1 . A method for treating cancer in a subject in need thereof, comprising administering a composition comprising isolated bacteria selected from at least two species wherein the bacteria from the first species comprise a 16S rDNA sequence having at least 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 1, and the bacteria from the second species comprise a 16S rDNA sequence having at least 98.7% sequence identity with a nucleic acid sequence according to SEQ ID NO: 2 wherein said subject is receiving, has received or will receive therapy with an immune checkpoint inhibitor, thereby treating the cancer. 
     
     
         2 . The method according to  claim 1 , wherein said composition further comprises one or more bacteria comprising a 16S rDNA sequence selected from SEQ ID NOs: 3 to 15 or a sequence having at least 98.7% sequence identity thereto. 
     
     
         3 . The method according to  claim 1 , wherein said composition further comprises bacteria from 7 different bacterial species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NO: 3 to 15 or a sequence having at least 98.7% sequence identity thereto. 
     
     
         4 . The method according to  claim 1 , wherein said composition further comprises bacteria from 4 different bacterial species wherein said bacteria comprise a 16S rDNA sequence selected from SEQ ID NO: 3 to 15 or a sequence having at least 98.7% sequence identity thereto. 
     
     
         5 . The method according to  claim 1 , wherein the cancer is selected from melanoma, bone cancer, pancreatic cancer, skin cancer, cancer of the head or neck, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, testicular cancer, breast cancer, brain cancer, carcinoma of the fallopian tubes, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal gland, kidney cancer, sarcoma of soft tissue, cancer of the urethra, cancer of the bladder, renal cancer, lung cancer, non-small cell lung cancer, thymoma, urothelial carcinoma leukemia, prostate cancer, mesothelioma, adrenocortical carcinoma, lymphomas, gastric cancer, and multiple myelomas. 
     
     
         6 . The method according to  claim 5 , wherein the melanoma is Harding-Passey melanoma, juvenile melanoma, lentigo maligna melanoma, malignant melanoma, acral-lentiginous melanoma, amelanotic melanoma, benign juvenile melanoma, Cloudman's melanoma, S91 melanoma, nodular melanoma, subungual melanoma, cutaneous melanoma, uveal/intraocular melanoma, superficial spreading melanoma, or cutaneous or intraocular malignant melanoma. 
     
     
         7 . The method according to  claim 1 , wherein the immune checkpoint inhibitor inhibits PD-1, PD-L1, TIM-3 or CTLA-4 activity. 
     
     
         8 . The method according to  claim 1 , wherein the immune checkpoint inhibitor is an anti PD-1, PD-L1, TIM-3 or CTLA-4 antibody. 
     
     
         9 . The method according to  claim 1 , wherein the immune checkpoint inhibitor is selected from nivolumab, pembrolizumab, cemiplimab, avelumab, durvalumab, atezolizumab, Spartalizumab, Camrelizumab, Sintilimab, Tislelizumab, Pidilizumab, Toripalimab, Ipilimumab or Tremelimumab. 
     
     
         10 . The method according to  claim 1 , wherein the immune checkpoint inhibitor is an interfering nucleic acid molecule, a small molecule or a PROteolysis TArgeting Chimera (PROTAC). 
     
     
         11 . The method according to  claim 1 , wherein the composition is administered by oral administration or rectal administration. 
     
     
         12 . The method according to  claim 1 , wherein the composition is in the form of a capsule, tablet, gel or liquid. 
     
     
         13 . The method according to  claim 1 , wherein the subject has received prior anti-cancer therapy with an immune checkpoint inhibitor. 
     
     
         14 . The method according to  claim 1 , wherein the immune checkpoint inhibitor is administered before, after or at the same time as the bacterial composition. 
     
     
         15 . The method according to  claim 1 , wherein the composition comprises live, attenuated or killed bacteria. 
     
     
         16 . The method according to  claim 1 , wherein the composition is lyophilised. 
     
     
         17 . The method according to  claim 1 , wherein the composition does not comprise bacterial spores. 
     
     
         18 . The method according to  claim 1 , further comprising surgical, radiation, and/or chemotherapeutic cancer intervention or administration of a second anti-cancer therapeutic. 
     
     
         19 . The method according to  claim 1 , wherein the subject has been determined to be a non-responder to the previous anti-cancer treatment with a checkpoint inhibitor. 
     
     
         20 . The method according to  claim 1 , wherein the subject has been determined to have a microbial profile in the gut microbiome with a low abundance of one or more bacteria comprising a 16S rDNA sequence selected from SEQ ID NOs: 1 to 15 or a sequence having at least 98.7% sequence identity thereto compared to a reference value.